Capsaicin inhibits the production of tumor necrosis factor α by LPS‐stimulated murine macrophages, RAW 264.7: a PPARγ ligand‐like action as a novel mechanism

Abstract

Capsaicin, a major ingredient of hot pepper, is considered to exhibit anti‐inflammatory properties. Our previous study demonstrated that capsaicin inhibited the production of pro‐inflammatory mediators through NF‐κB inactivation in LPS‐stimulated macrophages. In order to further clarify the mechanism underlying the anti‐inflammatory action of capsaicin, we investigated whether capsaicin alters PPARγ activity, which regulates the production of the pro‐inflammatory cytokine TNFα. Capsaicin significantly inhibited the production of TNFα by macrophages in a dose‐dependent manner. Simultaneous exposure of the cells to capsaicin and PPARγ agonist troglitazone or RXR agonist LG100268 resulted in stronger inhibition of TNFα production compared to the cells treated with either capsaicin, troglitazone, or LG100268 alone. Luciferase reporter assay revealed that capsaicin induced GAL4/PPARγ chimera and full length PPARγ (PPRE) transactivations in a dose‐dependent manner. Furthermore, a specific PPARγ antagonist T0070907 abrogated the inhibitory action of capsaicin on LPS‐induced TNFα production by RAW 264.7 cells, indicating that capsaicin acts like a ligand for PPARγ. Our data demonstrate for the first time that the anti‐inflammatory action of capsaicin may be mediated by PPARγ activation in LPS‐stimulated RAW 264.7 cells.